Role of extracellular glutamate measured by cerebral microdialysis in severe traumatic brain injury

Abstract

Object Authors of several studies have implied a key role of glutamate, an excitatory amino acid, in the pathophysiology of traumatic brain injury (TBI). However, the place of glutamate measurement in clinical practice and its impact on the management of TBI has yet to be elucidated. The authors’ objective in the present study was to evaluate glutamate levels in TBI, analyzing the factors affecting them and determining their prognostic value. Methods A prospective study of patients with severe TBI was conducted with an inclusion criterion of a Glasgow Coma Scale score ≤ 8 within 48 hours of injury. Invasive monitoring included intracranial pressure measurements, brain tissue PO2, jugular venous O2 saturation, and cerebral microdialysis. Patients received standard care including mass evacuation when indicated and treatment of elevated intracranial pressure values. Demographic data, CT findings, and outcome at 6 months of follow-up were recorded. Results One hundred sixty-five patients were included in the study. Initially high glutamate values were predictive of a poor outcome. The mortality rate was 30.3% among patients with glutamate levels > 20 µmol/L, compared with 18% among those with levels ≤ 20 µmol/L. Two general patterns were recognized: Pattern 1, glutamate levels tended to normalize over the monitoring period (120 hours); and Pattern 2, glutamate levels tended to increase with time or remain abnormally elevated. Patients showing Pattern 1 had a lower mortality rate (17.1 vs 39.6%) and a better 6-month functional outcome among survivors (41.2 vs 20.7%). Conclusions Glutamate levels measured by microdialysis appear to have an important role in TBI. Data in this study suggest that glutamate levels are correlated with the mortality rate and 6-month functional outcome.

Elevated glutamate and lactate predict brain death after severe head trauma

“…In contrast to our findings, Brown et al, 199825 showed that despite the persistent increase in the CSF glutamate levels up to 5 days after severe TBI, these changes did not predict brain death or correlate with GCS and electrophysiological deterioration. However, the majority of clinical studies indicate that increased brain extracellular glutamate levels in association with comorbidities may predict poor functional outcomes and brain death 11, 12, 13, 14. For instance, secondary mechanisms associated with the brain tissue deformation including global ischemia, sustained increased intracranial pressure and focal contusions11, 13, and spontaneous brain hypothermia (<36°C)26 have been implicated in the increase in glutamate levels and acute neuronal death.…”

“…Remarkably, high concentrations of extracellular glutamate are commonly observed after severe TBI, the magnitude of which correlates with increased intracranial pressure (ICP) and poor clinical outcomes 11, 12, 13, 14. Immediately after TBI, there is an exacerbated glutamate‐induced neuronal calcium influx and ionic imbalance, which evokes membrane depolarization and further glutamate release.…”

Disruptions in the Regulation of Extracellular Glutamate by Neurons and Glia in the Rat Striatum Two Days after Diffuse Brain Injury

“…Clinically, a multitude of studies have detected significant increases in extracellular glutamate levels in the days following injury, with some reports correlating increases in extracellular glutamate with unfavorable outcomes (Bullock et al, 1995Chamoun et al, 2010;Hlatky et al, 2004;Hutchinson et al, 2002;Koura et al, 1998;Persson and Hillered 1992;Reinert et al, 2000;Timofeev et al, 2011;Vespa et al, 1998;Yamamoto et al, 1999). These studies emphasize the significance of glutamate dysregulation in the acute pathophysiology and consequences of TBI.…”

The Role of Reactive Species in Epileptogenesis and Influence of Antiepileptic Drug Therapy on Oxidative Stress

“…Increased glutamate concentration in the extracellular compartment can be toxic to neurons [47]. Increase in the extracellular concentration of glutamate in the case of CNS injury or disease has been linked to a number of potential mechanisms including excessive release and impaired cellular uptake.…”